A number of minerals have been shown to be essential in animals, and an increasing number of deficiency syndromes are becoming recognized in humans. Long-term total parenteral nutrition allowed trace element deficiency to be studied in controlled conditions; now trace elements are always added to long-term parenteral nutrition regimens. It is highly probable (but difficult to study because of multiple deficiencies) that trace-element deficiency is also a frequent accompaniment of all PEM states.

Iron

The daily RNI for men is 160 μmol (8.7 mg) and for women 260 μmol (14.8 mg). Iron deficiency is common world-wide, affecting both developing and developed countries. It is particularly prevalent in women of a reproductive age. Dietary iron overload is seen in South African men who cook and brew in iron pots.

Copper

The daily RNI of copper is 1.2 mg (19 μmol). Shellfish, legumes, cereals and nuts are good dietary sources.

Deficiency

Menkes' kinky hair syndrome is a rare condition caused by malabsorption of copper. The Menkes' disease gene (ATP7A) encodes a copper-transporting ATPase and has a homology to the gene in Wilson's disease. Infants with this sex-linked recessive abnormality develop growth failure, mental retardation, bone lesions and brittle hair. Anaemia and neutropenia also occur. This condition, which serves as a model for copper deficiency, supports the idea that some of the clinical features seen in PEM are due to copper deficiency. Breast and cow's milk are low in copper, and supplementation is occasionally necessary when first treating PEM.

Zinc

The daily RNI of zinc is 9.5 mg (145 μmol) for men, 7 mg (110 μmol) for women and it is widely available in food. Zinc is involved in many metabolic pathways, often acting as a coenzyme; it is essential for the synthesis of RNA and DNA.

Deficiency

Acrodermatitis enteropathica is an inherited disorder caused by malabsorption of zinc. Infants develop growth retardation, severe diarrhoea, hair loss and associated Candida and bacterial infections. This condition provides a model for zinc deficiency. Zinc supplementation results in a complete cure. Deficiency probably also plays a role in PEM.

Zinc levels have been shown to be low in some patients with malabsorption or skin disease, and in patients with AIDS, but the exact role of zinc in these situations is disputed. Zinc has low toxicity, but high zinc levels from water stored in galvanized containers interfere with iron and copper metabolism. Wound healing is impaired with moderate zinc deficiency and is improved by zinc supplements. Impaired taste and smell, hair loss and night blindness are also features of severe zinc deficiency.

Iodine

The daily RNI of iodine is 140 μg (1.1 μmol) for men and women, and it is found in milk, meat and seafoods.

It exists in foodstuffs as inorganic iodides which are efficiently absorbed. Iodine is a constituent of the thyroid hormones

Deficiency

Many mountainous areas throughout the world lack iodine in the soil, and so iodine deficiency, which impairs brain development, is a WHO priority. Endemic goitre occurs in remote areas where the daily intake is below 70 μg, and in those parts 1-5% of babies are born with cretinism. In these areas, iodized oil should be given intramuscularly to all reproductive women every 3-5 years. In developed countries, salt is iodized and endemic goitre has disappeared.

Fluoride

In areas where the level of fluoride in drinking water is less than 1 p.p.m. (0.7-1.2 mg/L), dental caries is relatively more prevalent. Fluoridation of the water provides 1-2 mg daily, resulting in a reduction of about 50% of tooth decay in children. There is little fluoride in food except for seafish and tea, the latter providing 70% of the daily intake. Fluoride-containing toothpaste may add up to 2 mg a day.

Excessive fluoride intake in areas where the water fluoride level is above 3 mg/L can result in fluorosis, in which there is infiltration into the enamel of the teeth, producing pitting and discoloration.

Selenium

Clinical deficiency of selenium is rare except in areas of China where Keshan disease, a selenium-responsive cardiomyopathy, occurs. Selenium deficiency may also cause a myopathy. Toxicity has been described with very high intakes.

Calcium

In the UK, the daily RNI of calcium is 700 mg (17.5 mmol), but substantially higher values are now recommended in the USA. It is found in many foodstuffs, with two-thirds of the intake coming from milk and milk products, only 5% from vegetables. In the UK most flour is fortified. Calcium absorption from the gastrointestinal tract is vitamin D-dependent. Ninety-nine per cent of body calcium is in the skeleton.

Increased calcium is required in pregnancy and lactation, when dietary intake must be increased. Calcium deficiency is usually due to vitamin D deficiency.

Phosphate

The daily RNI of phosphate is the same as that of calcium, i.e. 17.5 mmol. Phosphates are present in all natural foods, and dietary deficiency has not been described. Patients taking large amounts of aluminium hydroxide can, however, develop phosphate deficiency owing to binding in the gut lumen. It can also be seen in total parenteral nutrition. Symptoms include anorexia, weakness and osteoporosis.

Other trace elements

The possible significance of cadmium, chromium, cobalt, manganese, molybdenum, nickel and vanadium